BioWorld International Correspondent
To-BBB Technologies BV raised €4 million (US$5.4 million) in a Series A round to finance the development of its technology for delivery of drugs across the blood-brain barrier and into the central nervous system. The company is preparing to move its lead development program, a drug treatment for Japanese encephalitis virus (JEV), into the clinic around a year from now.
The newly raised cash, which came from Amsterdam, the Netherlands-based Aescap Venture Management BV, will fund the company for about two years, to-BBB CEO and co-founder Peter Gaillard told BioWorld International. By then, it aims to have taken its lead program through a Phase IIa clinical trial.
Leiden, the Netherlands-based to-BBB Technologies has raised €1.1 million in seed funding since it was spun out in 2003 from the Blood-Brain Barrier Research Group, headed by company co-founder Bert de Boer at the University of Leiden. The company is commercializing a proprietary delivery method that exploits an existing receptor-mediated endocytosis process within the endothelial cells that line the brain's vasculature.
The particular receptor that is targeted is the Diphtheria toxin receptor, which, the company said, is expressed constitutively on the blood-brain barrier and on neurons and glial cells within the brain. To-BBB is using a modified form of the Diphtheria toxin, which lacks the toxic elements of the native protein, to deliver its payload - a liposome containing the antiviral drug ribavirin.
Ribavirin, a generic drug, has proven efficacy against JEV, which is endemic in Southeast Asia, where up to 50,000 cases are reported each year. Although it can cross the blood-brain barrier without a specific delivery method, attaining a therapeutically effective dose is a lengthy process. "It takes weeks of dosing before you get to that level," Gaillard said. By that time, the virus will have done its damage. It has a high fatality rate, and survivors often suffer from neurological complications.
To-BBB aims to slash the time needed to deliver an effective dose from weeks to days. It will conduct clinical trials in Southeast Asia, via a CRO that already is active in the region in testing anti-HIV compounds. The company estimates that the JEV therapy can deliver peak sales of €96 million. If successful, it will pursue other indications with the same therapy. "It's a broad spectrum antiviral drug. It can work for many other viruses in the brain," Gaillard said.
The other elements of to-BBB's JEV therapy are, like ribavirin, also well known, and have been the subject of extensive clinical research. "The components are already on the market," Gaillard said. However, its delivery strategy is novel and proprietary to the company, he added.
To-BBB is not the only firm operating in the area of drug delivery across the blood-brain barrier, Gaillard said, although it remains at an early stage of development. "There's not a lot of real pharmacological knowledge on the blood-brain barrier in terms of targeting and drug delivery," he said. Competitive approaches are all at the preclinical stage as well, he said, and the international scientific community involved in the area is small, numbering only about 200 scientists. "It's really more or less a neglected field still."